Journal article
Inflammatory Chemokine Transport and Presentation in HEV: A Remote Control Mechanism for Monocyte Recruitment to Lymph Nodes in Inflamed Tissues
The Journal of experimental medicine, Vol.194(9), pp.1361-1374
11/05/2001
DOI: 10.1084/jem.194.9.1361
PMCID: PMC2195988
PMID: 11696600
Abstract
Interstitial fluid is constantly drained into lymph nodes (LNs) via afferent lymph vessels. This conduit enables monocyte-derived macrophages and dendritic cells to access LNs from peripheral tissues. We show that during inflammation in the skin, a second recruitment pathway is evoked that recruits large numbers of blood-borne monocytes to LNs via high endothelial venules (HEVs). Inhibition of monocyte chemoattractant protein (MCP)-1 blocked this inflammation-induced monocyte homing to LNs. MCP-1 mRNA in inflamed skin was over 100-fold upregulated and paralleled MCP-1 protein levels, whereas in draining LNs MCP-1 mRNA induction was much weaker and occurred only after a pronounced rise in MCP-1 protein. Thus, MCP-1 in draining LNs was primarily derived from inflamed skin. In MCP-1
−/
− mice, intracutaneously injected MCP-1 accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was transported via the lymph to the luminal surface of HEVs where it triggered integrin-dependent arrest of rolling monocytes. These findings demonstrate that inflamed peripheral tissues project their local chemokine profile to HEVs in draining LNs and thereby exert “remote control” over the composition of leukocyte populations that home to these organs from the blood.
Details
- Title: Subtitle
- Inflammatory Chemokine Transport and Presentation in HEV: A Remote Control Mechanism for Monocyte Recruitment to Lymph Nodes in Inflamed Tissues
- Creators
- Roger T. Palframan - Harvard UniversitySteffen JungGuiying Cheng - Harvard Medical SchoolWolfgang Weninger - Harvard UniversityYi Luo - Harvard UniversityMartin Dorf - Harvard UniversityDan R. Littman - New York UniversityBarrett J. Rollins - Dana-Farber Cancer InstituteHans Zweerink - MSDAntal RotUlrich H. von Andrian - Harvard University
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.194(9), pp.1361-1374
- Publisher
- The Rockefeller University Press
- DOI
- 10.1084/jem.194.9.1361
- PMID
- 11696600
- PMCID
- PMC2195988
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 11/05/2001
- Academic Unit
- Urology
- Record Identifier
- 9984320070002771
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